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Simultaneous neural ensemble recordings of pain in the cerebral cortex of behaving rats

Simultaneous neural ensemble recordings of pain in the cereb...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jun CHEN~(1,2) 1 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china 2 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi''an 710038,china

＜正＞Objective In the past 10 years,a technique allowing simultaneous,multisite and many neuron recordings in freely moving and behaving animals（e.g.,monkeys,rats and mice） and even in human subjects has been well developed and successfully applied in many regions of the *** state-of-the-art technique of in vivo simultaneous multisite recordings of neural ensemble responses in the brain enables a good combination with various behavioral assays in freely moving and behaving *** this report,I would like to introduce the use of this technique in study of pain in the cerebral cortex of behaving *** Microwire electrode arrays（2x4 or 2x8） were implanted into the target brain area of a rat in the aid of stereotaxic surgical *** at least 7 days of recovery, simultaneous recordings of cerebral cortical neural ensemble responses in a behaving rat were carried out using the Plexon multichannel Acquisition Processor（MAP） system and an overhead video tracker system processed by Plexon CinePlex software that enables continuous real-time behavioral tracking and synchronization of video and neural signals through interaction with the MAP system.A Plexon MAP system receives and processes the pre-amplified and filtered neural ensemble signals by RASPUTIN Software for online displaying,sorting,recording and synchronizing of the neural ensemble *** nociceptive stimuli,including mechanical,thermal and chemical modalities,were applied to the rat’s *** Long-term unitary stability was confirmed by various statistical analyses. Nociceptive neuronal units were identified by online or offline sorting from the primary somatosensory（S1） cortex and the motor cortex（MCx）.The neuronal units identified in the S1 area were wide-dynamic-range（WDR） and nociceptive-specific（NS） in nature,while those in the MCx were also responsive to noxious *** neural ensemble responses can be significantly changed by peripheral inflammatory pain state tha

关键词： simultaneous neural ensemble recordings pain cerebral cortex behaving animals

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Altered locomotor and exploratory behaviors of rats caused by subcutaneous bee venom injection:open field test

Altered locomotor and exploratory behaviors of rats caused b...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Dan LU~1,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china 2 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi''an 710038,china

＜正＞Background:pain is usually considered to be a complex phenomenon,which requires the scoring of several behavioral *** pathological state,persistent or chronic pain can affect various higher brain functions and lead to emotional *** open field test is usually used to study the emotional state,the effect of various pharmacological agents,biological/physical environmental factors,and the impact of chronic pain on emotional ***,the spontaneous behavioral responses induced by peripheral persistent inflammatory pain in the open field were rarely ***:In this report,we investigated the altered behavioral responses induced by hind-paw bee venom（BV） injection and the relationship between pain-related behaviors and spontaneous responses in the open ***:Male Sprague-Dawley albino rats were randomly divided into four groups:naive,saline,BV-inflamed,bupivacaine-pretreated BV-inflamed *** the open field test,the spontaneous behavioral responses of the rats in these four groups were clearly and long-term ***: It was found that BV-induced persistent nociception can reduce the locomotor and exploratory behavioral responses. The BV-inflamed group also has a significantly increased traveled distance in four corners and decreased traveled distance in center and four *** addition,these altered spontaneous pain-related responses in open field can be reversed by ***:We demonstrated that bee venom induced persistent nociception can elicit alteration of spontaneous behavioral responses in open field which is relevant to pain-related behavior directly.

关键词： open field test spontaneous behavioral responses persistent nociception bee venom test

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Effects of peripheral nociception on neural activities of motor cortex in rats:in vivo multi-channel recordings

Effects of peripheral nociception on neural activities of mo...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Chang-Ming WANG~1,Lei YANG~1,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china 2 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi''an 710038,china

＜正＞Objective:The present study was designed to investigate the effects of subcutaneous saline or bee venom injection on responses of the motor cortical neurons and those of behaviors in conscious,behaving ***:We examined the motor cortical neuronal activation with an in vivo multi-channel recording technique before and after saline or bee venom was delivered subcutaneously（s.c.） into the plantar surface of the hind paw contralateral to the recording ***:A total of 81 single neurons were recorded in the motor *** first analyzed the spatial sequence *** saline-induced phasic pain state,29（36%） neurons showed significant excitatory responses,whereas 19（23%） displayed significant inhibitory *** bee venom-induced tonic pain state,52（64%） indicated significant excitatory responses,however,7（9%） showed inhibitory *** then analyzed the temperoal sequence *** terms of saline-induced phasic nociception,a sharp increase of spike discharges at the start of saline injection was *** terms of bee venom-induced tonic pain state,the increase of spike discharges was during the initial half hour after *** venom ***:The present result,a microcosmic view of the brain pain-related responses,accorded well with the results of neuroimaging studies,a macroscopic view of the brain pain-related responses,indicating the role of the motor cortex in the information processing of pain.

关键词： bee venom neural ensemble coding pattern tonic nociception phasic nociception motor cortex

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Imbalance between excitatory and inhibitory synaptic transmission in the primary somatosensory cortex caused by persistent nociception

Imbalance between excitatory and inhibitory synaptic transmi...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Fa-Le CAO~1,Rui-Rui WANG~1,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi’an 710038,china 2 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china

Objective:There is substantial evidence supporting the notion that the primary somatosensory cortex (S1) is an important structure involved in the perceptional component of ***,neuronal circuit and synaptic plasticity occurring within the S1 after injury has been proposed to contribute substantially to the pathophysiogenesis of chronic ***,few reports have been conducted to simultaneously investigate synaptic plasticity in the S1 in response to persistent pain at cellular and network *** present study was thus undertaken to evaluate,at the local network level,potential changes in synaptic connection and transmission in the S1 following peripheral persistent nociception in ***:Periphery subcutaneous injection of bee venom (BV) was used to mimic the state of persistent *** initial probe of underlying mechanisms was attempted at the neuronal circuit level by using multi-electrode array recording(MED-64).In electrophysiological experiments, typical neocortical neurons characterized by morphology and action potential were applied to obtain the spontaneous and miniature excitatory and inhibitory post-synaptic currents(EPSC/IPSC).Furthermore,immunohistochemistry and Western blotting were performed to investigate the changes of AMPA and GABA receptors in the state of peripheral persistent ***:By using MED-64 coupled with two-dimensional current source density imaging, we found that persistent pain produced enlargement of synaptic connection size in the S1 slice,reflecting increased spatial plasticity by ***,compared with saline control,significant increase was also found in the temporal plasticity,namely long-term *** slice patch clamp recordings on identified S1 neurons demonstrated that both of the amplitude and frequency of spontaneous and miniature EPSC were greatly increased, while the amplitude of spontaneous and miniature IPSC was markedly decreased after BV ***,the half-width

关键词： primary somatosensory cortex synaptic plasticity AMPA receptor GABA receptor bee venom test

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Antinociceptive effects of rapamycin on nociception and pain hypersensitivity:roles of mTOR signaling pathway?

Antinociceptive effects of rapamycin on nociception and pain...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Dan LV~1,Yan WANG~2,Chun-Li LI~2,Fan YANG~2,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china 2 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi''an 710038,china

＜正＞Objective Mammalian target of rapamycin（mTOR） is a key regulator of mRNA translation which can be modified in a wide range of pathological *** studies indicated that mTOR was likely to be involved in the pathological process of pain hypersensitivity and neuronal *** the present report,we evaluate whether rapamycin is effective in antinociception and anti-hyperalgesia or anti-allodynia caused by subcutaneous injection of whole bee venom（BV）.Methods Rapamycin,a mTOR inhibitor,was administrered by intrathecal（i.t.） administration and intraplantar（***.） administration in conscious *** behavioral tests,persistent spontaneous nociceptive reflex was quantified by counting the number of paw flinches,heat hyperalgesia was quantified by measuring paw withdrawal thermal latency（PWTL） to radiant heat and mechanical hyperalgesia was quantified by measuring paw withdrawal threshold （PWMT） to von Frey *** *** of rapamycin（0.125,1.25 and 12.5μg） resulted in a doserelated suppression of the BV-induced persistent paw flinches,heat hypersensitivity,and mirror-image heat（MIH） hypersensitivity,but without any effectiveness on mechanical ***,*** of rapamycin （0.125,1.25 and 12.5μg） resulted in a dose-related suppression of the BV-induced persistent paw flinches,heat hypersensitivity,and mirror-image heat（MIH） hypersensitivity,but without any effectiveness on mechanical *** mTOR signaling pathway might be involved in pathophysiological processing associated with BV-induced nociception and inflammatory pain at both spinal and peripheral levels.

关键词： mammalian target of rapamycin(mTOR) persistent nociception pain hypersensitivity bee venom test

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Quantitative evaluation of dose-effect of subcutaneous injection of bee venom on persistent nociception,pain hypersensitivity and inflammatory responses in rats

Quantitative evaluation of dose-effect of subcutaneous injec...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jia-Rui ZHANG~1,Yun-Fei LV~1,Yan WANG~1,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,The fourth military medical university,xi''an 710038,china 2 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china

＜正＞Objective The bee venom test has long been used to evaluate the antinociceptive,antihyperalgesic and anti-inflammatory effects of endogenous and exogenous substances,however,the dose-effect of subcutaneous（s.c.） injection of bee venom on each pain-related behavior has not been ***,in the current report we used six doses（0.001,0.005,0.01,0.05,0.1,and 0.2 mg in 50 uL）of bee venom solution to see whether there are differences in *** Quantitative methods were used for evaluation of each pain-related *** the number of paw flinches of each 5-min time block from 0-60 min was used to evaluate the intensity of persistent spontaneous nociception,while paw withdrawal thermal latency（PWTL,s）and paw withdrawal mechanical threshold （PWMT,g）were used to evaluate thermal and mechanical hyperalgesia,*** of paw volume, cross-dimensional paw thickness,skin temperature and volume of plasma extravasation were used to evaluate local inflammatory *** Generally,there were significant differences in peak responses between persistent spontaneous nociception,PWTL,PWMT,and local inflammation following *** of bee ***, there was a dose-dependent effect of bee venom on the number and time period of paw flinches,and the dose-effect curve showed a typical ’S’ that reached plateau at 0.1 ***,the peak%maximal possible effect（MPE）of bee venom on the reduction in PWTL and PWMT at 2 h after injection was caused by different doses of bee venom, namely 0.05 mg for PWTL and 0.01 mg for *** results suggest that the dose required for%MPE is different from each other in terms of persistent spontaneous nociception,thermal hyperalgesia and mechanical hyperalgesia. Furthermore,the dose for%MPE of four quantitative measurements was also different between paw volume（or thickness）,plasma extravasation and skin *** dose of 0.1 mg was required for%MPE of both paw volume and paw thickness,wh

关键词： bee venom test dose-effect persistent spontaneous nociception thermal hyperalgesia mechanical hyperalgesia local inflammation

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Gene profiling in dynamic regulation of structure and function of lifespan CNS myelin sheath

Gene profiling in dynamic regulation of structure and functi...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Fang xiE~1,Han FU~1,Lei YANG~2,Bian-Ling ZHANG~1,Fu-Kang ZHANG~2,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi''an 710038,china 2 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china

＜正＞Objective Myelin sheath is an important structure for a neuronal axon fiber to perform rapid conduction of action potentials in both PNS and CNS that help to realize various brain ***,it has been rarely known that there is a dynamic homeostasis among myelination,demyelination and remyelination to maintain the compact myelin sheath intact in *** aim of this study is to establish a novel structure-function-genome model for unravelling the molecular and cellular mechanisms underlying this rarely-known dynamic,lifespan phenomena in brain *** Electron microscopic quantitative（qEM） analysis and conduction velocity（CV） of nerve projection tract were used to evaluate ultrastructural and functional changes in myelin sheath of the CNS with age from postnatal day（PND） 1 to 600. Gene microarray and RT-PCR technique were used to monitor age-related changes in gene expression profiling of the CNS. Cluster analysis and gene ontology were used for identification of known and unknown genes involved in age-related changes in myelin sheath of *** Along lifespan,dynamic changes in myelination,demyelination and remyelination were clearly observed by qEM *** example,myelination began to occur in several single fibers around PND 7-9,dramatically increased（about 75%） around PND 21 and reached maturity（100%） around PND 28. Demyelination was shown to occur around PND 56 and became dramatic when aging（around PND 400-600）.These agerelated dynamic changes in myelin sheath were parallel with functional changes in *** explore whether there is functional genomic regulation of myelin sheath along lifespan,optic nerves from which genes expressed in neuronal cell bodies can be completely avoided were removed freshly and subjected to gene microarray hybridization（Agilent Technology）. Briefly,673 transcripts were significantly associated with myelin change with age and could be divided into four clusters: （1） age-related up-regulation genes

关键词： gene profiling dynamic homeostasis lifespan age myelin sheath

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Roles of TRPC3/6/7 channels in a rat model of inflammatory pain

Roles of TRPC3/6/7 channels in a rat model of inflammatory p...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Jing DING~1,xiu-Yu CUI~1,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china 2 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi’an 710038,china

Background:The transient receptor potential canonical(TRPC) channels,which are abundantly expressed in central nervous system(CNS),are Ca permeable nonselective cation channels with different biological *** studies indicated that TRPC1 and TRPC6 channels were likely to be involved in the pathological process of mechanical hyperalgesia and nociceptor *** whether TRPC channels are involved in melittin- or formalin-induced inflammatory nociceptive responses remains ***:In this study,we used behavioral tests combined with pharmacological manipulations to explore the potential roles of TRPC channels in inflammatory pain and ***:In this study,we used the well-established bee-venom(melittin) and formalin *** flinch test was to examine whether TRPC channels are involved in inflammatory paininduced primary *** pain sensitivity of rats was determined by testing paw withdrawal thermal latency(PWTL,s) in response to heat stimuli applied to the injected *** pain hypersensitivity was tested as the paw withdrawal mechanical threshold(PWMT,g).Results:Post- and pre-treatment of the primary injury site with *** of SKF96365,a TRPC3/6/7 antagonist,significantly suppressed the development of inflammatory pain-evoked persistent spontaneous nociception(PSN) and hypersensitivity(thermal and mechanical). Whereas local administration of SKF96365 into the contralateral hindpaw produced no significant effect on any of the pain-associated *** together,these data indicate that TRPC3/6/7 channels might be involved in pathophysiological processing associated with inflammatory ***:In conclusion,we demonstrated for the first time that,although SKF96365 do not affect baseline thermal latency and mechanical nociceptive threshold,it reversed the inflammatory pain-induced spontaneous nociception,heat and mechanical hyperalgesia, indicating that TRPC3/6/7 channels might pla

关键词： TRPC channels melittin formalin test persistent spontaneous nociception primary thermal hyperalgesia primary mechanical hyperalgesia

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Activation of rat primary afferent nociceptive neurons by formaldehyde and mediating roles of the vanilloid receptor TRPV1

Activation of rat primary afferent nociceptive neurons by fo...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Yong xiAO~1,Li-Juan TIAN~2,Yi-Ru DU~2,Zhuo-Min LU~1,Yao-Qing YU~1,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,fourth military medical university,xi’an 710038,china 2 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china

Background The formalin test is a commonly used animal model of acute and tonic pain,however,the biological actions of formaldehyde(FA,the main ingredient of the formalin solution) on primary nociceptor cells remain *** this report,effects of FA on electrophysiologically-identified primary nociceptor cells were evaluated in vitro and the roles of the vanilloid receptor TRPV1 in FA-produced activation of primary nociceptors were also examined at both cellular and behavioral *** Of 92 acutely dissociated DRG cells recorded by current patch-clamp,34%were discharged after FA application(50 s) with various latencies of the first action potential(Aβ) *** FA-sensitive cells were small to medium-sized(diameters:17.5-37.5μm) and identified electrophysiologically as nociceptor cells due to the unique characteristic of their Aβwaveform with a hump on the repolarizing *** FA-evoked Aβfrequency was concentration-dependent within a range less than 0.004%.Co-application of capsazepine(CPZ,5μM),a competitive antagonist of TRPV1 receptors,could block FA-evoked firing but without influence on the membrane depolarization of all cells tested(n=8).Of another 160 cells examined by confocal calcium imaging,32%(51 cells with diameters:17.5-32.5μm) were shown to respond to FA with an intracellular Ca *** 51 FA-sensitive cells,67%were suppressed by CPZ with the remaining 33%unaffected,suggesting partial involvement of TRPV1 in mediation of the FA-evoked intracellular Ca rise. In comparison with controls(n=5),the FA-evoked inward current recorded by voltage-clamp could also be significantly suppressed by CPZ(n=9).Finally,local effects of two doses of CPZ were also confirmed in the formalin behavioral test and it was shown that the formalin-induced paw flinches in both phase I and phase II were partially but significantly suppressed by ***(1) FA can activate a subpopulation of primary nociceptor cells by membrane depolarization and firing of action

关键词： formalin test nociceptor TRPV1 receptor dorsal root ganglion patch clamp calcium imaging

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Metabotropic glutamate receptor subtype 1 and 5 mediate opposite effects on pain-related spatial and temporal synaptic plasticity in rat hippocampal formation:Multi-electrode array recordings

Metabotropic glutamate receptor subtype 1 and 5 mediate oppo...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yan WANG~1,Ming-Gang LIU~2,Dan LV~2,Rui-Rui WANG~1,Xue-Feng CHEN~1,Fu-Kang ZHANG~2,xiu-Yu CUI~2,Jun CHEN~(1,2,*) 1 institute for biomedical sciences of pain and institute for functional brain disorders,tangdu hospital,The fourth military medical university,xi''an 710038,china 2 institute for biomedical sciences of pain,Capital medical university,Beijing 100069,china

＜正＞Objective It has been revealed that peripheral persistent nociception results in spatial and temporal synaptic plasticity in rat hippocampal formation（HF）,however,the underlying mechanisms are still *** the present report,we present a line of evidence implicating opposing roles of metabotropic glutamate receptor（mGluR） subtype 1 and 5 in mediation of pain-related spatial and temporal synaptic plasticity in the *** Inhibitors targeting mGluRl and mGluR5 were used,*** and temporal components of entorhinal-hippocampal synaptic connections and efficacy of rats were recorded by using a newly developed 64-channels（8×8）multi-electrode array technique（Med64 system）.Results（1）Pharmacological inhibition of mGluR5 activation,at the plateau phase of the long-term potentiation（LTP）,effectively decreased pain-enhanced hippocampal long-term potentiation（LTP） maintenance,while similar blockade of mGluRl resulted in an even higher level of potentiation.（2）The mGluR subtype-related difference was also detected when analyzing effects of these two drugs on the spatial amplification of pain,with no clear involvement of mGluR5 and a negative modulation exerted by *** These findings suggest differential and even contradictory roles of mGluRl and mGluR5 in pain-associated spatial and temporal plasticity of synaptic *** importantly,this maybe the first demonstration for a subtype-linked functional separation/opposition regarding roles of group I mGluRs in higher levels of abnormal pain processing in the HF.

关键词： persistent pain hippocampal formation synaptic plasticity multi-electrode array metabotropic glutamate receptor

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